methyl 2-(3-chlorophenyl)acetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-chlorophenylacetic acid (21.76 g, 127.6 mmol) in dichloroethane (100 ml) was added MeOH (15.6 ml, 383 mmol) and H2SO4 (1 ml) at room temperature. After 20 minutes stirring, the mixture was heated at 80° C. for 2 h. The reaction mixture was poured into ice water and extracted with CHCl3. The combined extracts were washed with aq NaHCO3 and brine. After dried over Na2SO4, the extract was concentrated in vacuo to give methyl 3-chlorophenylacetate (25.4 g, 100%) as a colorless oil. 1H-NMR (CDCl3) δ3.60 (s, 2H), 3.70 (s, 3H), 7.15-7.26 (m, 4H). extracted with CHCl3 The combined extracts were washed with aq NaHCO3 and brine After dried over Na2SO4 the extract was concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (3-chloro-phenyl)acetic acid methyl ester (5.0 g, 27.1 mmol, commercially available) in concentrated sulfuric acid (7.5 mL, 140.7 mmol) at 0° C. was added drop-wise nitric acid (2.52 g, 70%, 28.0 mmol). After stirring at 0° C. for two hrs, the reaction mixture was poured into ice water and was extracted into dichioromethane. The organic extract was washed with brine, dried (anhydrous sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography over silica gel eluting with 6% ethyl acetate in hexane to give the desired (3-chloro-4-nitro-phenyl)acetic acid methyl ester as an oil (2.1 g,33%), and (5chloro-2-nitro-phenyl)acetic acid methyl ester as an oil (3.2 g, 51%). 1H NMR (CDCl3) δ: 3.69 (s, 2H), 3.74 (s, 3H), 7.33 (dd, 1H, J=8.4 Hz, 1.9 Hz), 7.50 (d, 1H, J=1.8 Hz), 7.87 (d, 1H, J=8.4 Hz. was extracted into dichioromethane The organic extract was washed with brine dried (anhydrous sodium sulfate) filtered concentrated under reduced pressure The residue was purified by flash column chromatography over silica gel eluting with 6% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of dimethyl methylphosphonate (17.93 g, 144 mmol) in THF (270 mL) at −78° C. was slowly added n-BuLi (2.5M, 64.2 mL, 160.6 mmol). The reaction mixture was stirred for 1 h and (3-chloro-phenyl)-acetic acid methyl ester (26.93 g, 146 mmol) was slowly added. The reaction mixture was allowed to warm to room temperature and was stirred for 24 h. Acetic acid (15 mL) was added and the volatiles were removed in vacuo. The residue was diluted with CH2Cl2 and the organic solution was washed carefully with saturated aqueous NaHCO3 (3 times). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. Purification by medium pressure chromatography (20% EtOAc in hexanes to EtOAc) provided the title compound (9.28 g). at −78° C. was stirred for 24 h the volatiles were removed in vacuo The residue was diluted with CH2Cl2 the organic solution was washed carefully with saturated aqueous NaHCO3 (3 times) The organic layer was dried (MgSO4) filtered concentrated in vacuo Purification by medium pressure chromatography (20% EtOAc in hexanes to EtOAc)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-chlorophenylacetic acid (21.76 g, 127.6 mmol) in dichloroethane (100 ml) was added MeOH (15:6 ml, 383 mmol) and H2SO4 (1 ml) at room temperature. After 20 minutes stirring, the mixture was heated at 80° C. for 2 h. The reaction mixture was poured into ice water and extracted with CHCl3. The combined extracts were washed with aq. NaHCO3 and brine. After dried over Na2SO4, the extract was concentrated in vacuo to give methyl 3-chlorophenylacetate (25.4 g, 100%) as a colorless oil. 1H-NMR (CDCl3) δ 3.60 (s, 2H), 3.70 (s, 3H), 7.15–7.26 (m, 4H). extracted with CHCl3 The combined extracts were washed with aq. NaHCO3 and brine After dried over Na2SO4 the extract was concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-chlorophenylacetic acid (10.0 g) in methanol (80 ml) containing 2 drops of concentrated sulphuric acid was heated at reflux for 3 hours. The reaction mixture was concentrated and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was dried over magnesium sulphate and evaporated to give the title compound (9.8 g) as a colourless oil. was heated at reflux for 3 hours The reaction mixture was concentrated partitioned between ethyl acetate (100 ml) and water (100 ml) The organic phase was dried over magnesium sulphate evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (3-Chloro-phenyl)-acetic acid methyl ester (2.0 g, 10.8 mmol), N-bromosuccinimide (1.95 g, 11.0 mmol) and 3 drops of hydrobromic acid (48% solution) in chloroform (100 mL) was heated under reflux for three days. Additional amounts of N-bromosuccinimide and hydrobromic acid were added to drive the reaction to completion. The reaction mixture was concentrated to dryness, taken up in methylene chloride and loaded onto a column of silica gel. Elution with 10% ethyl acetate/hexanes gave Bromo-(3-chloro-phenyl)-acetic acid methyl ester (1.95 g, 69% yield) as a colorless oil. The NMR spectrum obtained on the sample is compatible with its structure. was heated under reflux for three days the reaction to completion The reaction mixture was concentrated to dryness Elution with 10% ethyl acetate/hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (3-Chloro-phenyl)-acetic acid methyl ester (2.0 g, 10.8 mmol), N-bromosuccinimide (1.95 g, 11.0 mmol) and 3 drops of hydrobromic acid (48% solution) in chloroform (100 mL) was heated under reflux for three days. Additional amounts of N-bromosuccinimide and hydrobromic acid were added to drive the reaction to completion. The reaction mixture was concentrated to dryness, taken up in methylene chloride and loaded onto a column of silica gel. Elution with 10% ethyl acetate/hexanes gave Bromo-(3-chloro-phenyl)-acetic acid methyl ester (1.95 g, 69% yield) as a colorless oil. The NMR spectrum obtained on the sample is compatible with its structure. was heated under reflux for three days the reaction to completion The reaction mixture was concentrated to dryness Elution with 10% ethyl acetate/hexanes